Dr. Yang?s long-term career goal is to pursue translational research in the development of novel therapies for the malignancies. His immediate term career objective is to explore antigendefined immunotherapeutic approaches for Epstein Barr virus (EBV)-associated malignancies. EBV(+) tumors offer a unique opportunity to develop antigendefined immunotherapeutic strategies because specific EBV antigens expressed in tumor cells can serve as validated targets for T cell mediated specific tumor killing. The overall objective of this proposal is to study methods of immune manipulation targeting EBV-associated tumors, specifically nasopharyngeal carcinoma (NPC) and Hodgkin?s disease (HD). Strategies to be pursued include: 1) an antigen-specific cell vaccine to induce or enhance specific T cell responses in patients with NPC; 2) ex vivo expansion of antigen-specific T cells from patients with HD or NPC using dendritic cells transduced with self-inactivating recombinant lentiviral vectors of interest; and 3) combination of in vivo vaccination and ex vivo expansion strategies in NPC patients. Success in ex vivo expansion will lead to an adoptive immunotherapeutic trial. These EBV-associated tumors are seen as models for other tumors in which tumor specific antigens have been identified and the development of novel therapeutic approaches.